The general long-term goal of this renewal application continues to be the elucidation of cellular and molecular mechanisms of regulation of the cardiovascular system. Our primary emphasis is on proteins and enzymes which govern the delivery, utilization, and exodus of calcium. The goal of most of the projects is the relationship of structure to function. The grant is divided into Missions which have stable long-term objectives and projects which have aims which may be completed or altered within a shorter period of time. Mission I, Pumps and Channels, emphasizes structural stu- dies on the Na+,K+-ATPase, the Mg2+-ATPase of the t-tubules and the calcium channel proteins using techniques of immunology, protein chemistry, and molecular genetics. Mission II, Electrophysiology, examines the effect of calcium channel modulators on vascular smooth muscle and skeletal muscle. Mission III, Contractile Proteins, has six projects which deal with the mechanism whereby smooth and striated muscle are regulated in the short term and/or how this regulation is altered in the long term by "remodeling" processes. Mission IV, Sarcoplasmic Reticulum, focuses on the rapid kinetic evaluation of the Ca2+-ATPase activity in cardiac and skeletal muscle sarcoplasmic reticulum and on the regulation of the Ca2+-ATPase in cardiac sarcoplasmic reticulum by phosphorylation/dephosphorylation of phospholamban. Mission V is composed of two projects which deal with vascular smooth muscle and blood vessel mechanisms through which vasodilator drugs may act. Mission VI has as its goals determination of the primary structure of the lipid transfer protein complex, definition of the structural features which regulate its activity and the identification of factors which regulate its production in liver. Six Cores, Cardiovascular Models, Protein Chemistry, Computer, Administrative, Molecular Biology and Immunology/ Monoclonal Antibodies serve eighteen projects in the six Missions.